Antitumor Effect of Embryonic Stem Cells in a Non-Small Cell Lung Cancer Model: Antitumor Factors and Immune Responses

被引:9
作者
Dong, Wei [1 ,2 ]
Qiu, Chen [1 ]
Shen, Hongchang [1 ]
Liu, Qi [1 ]
Du, Jiajun [1 ,2 ]
机构
[1] Shandong Univ, Shandong Prov Hosp, Inst Oncol, Jinan 250021, Peoples R China
[2] Shandong Univ, Shandong Prov Hosp, Dept Thorac Surg, Jinan 250021, Peoples R China
基金
中国国家自然科学基金;
关键词
embryonic stem cells; immunotherapy; antitumor immunity; antitumor factors; IN-VIVO; MICROENVIRONMENT; VACCINATION; ANTIGEN; MICE;
D O I
10.7150/ijms.6538
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Research in recent years has revealed that embryonic stem cells (ESCs) could generate obvious antitumor effects in both vitro and vivo. In vitro, ESCs could secrete soluble factors that are capable of blocking cancer cells proliferation, moreover, embryonic microenvironments could effectively inhibit tumorigenesis and metastasis; while in vivo, administration of ESCs in tumor-bearing mice could generate significant antitumor effects by indirectly activating the antitumor immune system. In this study, non-small cell lung cancer cells (Lewis Lung Carcinoma cells, LLCs) and ESCs were co-injected together into mice, after that subcutaneous tumor growth was monitored, cellular and humoral immune responses were detected, and different control groups were set to compare the results in different conditions. Our results suggested that compared to be injected alone, ESCs co-injected with cancer cells could inhibit cancer cell growth more efficiently in vivo, with more CD8+ lymphocytes generated in both peripheral circulation and spleen, and with higher serum anticancer cytokine level (interleukin (IL)-2 and interferon (IFN)-gamma). We conclude that the boosted antitumor effects induced by ESCs and cancer cells co-injection may be both the effects of antitumor factors secreted by ESCs and immune responses induced by ESCs in vivo.
引用
收藏
页码:1314 / 1320
页数:7
相关论文
共 39 条
[1]
CD8+T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells [J].
Antony, PA ;
Piccirillo, CA ;
Akpinarli, A ;
Finkelstein, SE ;
Speiss, PJ ;
Surman, DR ;
Palmer, DC ;
Chan, CC ;
Klebanoff, CA ;
Overwijk, WW ;
Rosenberg, SA ;
Restifo, NP .
JOURNAL OF IMMUNOLOGY, 2005, 174 (05) :2591-2601
[2]
IFN-γ Inhibits IL-4-Induced Type 2 Cytokine Expression by CD8 T Cells In Vivo and Modulates the Anti-Tumor Response [J].
Apte, Simon H. ;
Groves, Penny ;
Olver, Stuart ;
Baz, Adriana ;
Doolan, Denise L. ;
Kelso, Anne ;
Kienzle, Norbert .
JOURNAL OF IMMUNOLOGY, 2010, 185 (02) :998-1004
[3]
Targeted therapies to improve tumor immunotherapy [J].
Begley, Jonathan ;
Ribas, Antoni .
CLINICAL CANCER RESEARCH, 2008, 14 (14) :4385-4391
[4]
Transplanting stem cells: Potential targets for immune attack. Modulating the immune response against embryonic stem cell transplantation [J].
Boyd, AS ;
Higashi, Y ;
Wood, KJ .
ADVANCED DRUG DELIVERY REVIEWS, 2005, 57 (13) :1944-1969
[5]
Embryonic vaccines against cancer: An early history [J].
Brewer, Bradley G. ;
Mitchell, Robert A. ;
Harandi, Amir ;
Eaton, John W. .
EXPERIMENTAL AND MOLECULAR PATHOLOGY, 2009, 86 (03) :192-197
[6]
The Stem Cell Network model: clinical implications in cancer [J].
Cabanillas, Ruben ;
Llorente, Jose L. .
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY, 2009, 266 (02) :161-170
[7]
Chen BA, 2010, INT J NANOMED, V5, P593
[8]
Administration of embryonic stem cells generates effective antitumor immunity in mice with minor and heavy tumor load [J].
Dong, Wei ;
Du, Jiajun ;
Shen, Hongchang ;
Gao, Dongwei ;
Li, Zhenxiang ;
Wang, Guanghui ;
Mu, Xueru ;
Liu, Qi .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2010, 59 (11) :1697-1705
[9]
Human embryonic stem cells and their differentiated derivatives are less susceptible to immune rejection than adult cells [J].
Drukker, Micha ;
Katchman, Helena ;
Katz, Gil ;
Friedman, Smadar Even-Tov ;
Shezen, Elias ;
Hornstein, Eran ;
Mandelboim, Ofer ;
Reisner, Yair ;
Benvenisty, Nissim .
STEM CELLS, 2006, 24 (02) :221-229
[10]
Embryonic stem cells and the challenge of transplantation tolerance [J].
Fairchild, PJ ;
Cartland, S ;
Nolan, KF ;
Waldmann, H .
TRENDS IN IMMUNOLOGY, 2004, 25 (09) :465-470